title: Human chorionic gonadotropin increases β-cleavage of amyloid precursor protein in SH-SY5Y cells.
abstract: Elevated levels of amyloid-β (Aβ) peptides, the main component of amyloid plaques in Alzheimer's disease, are the result of excessive β- and γ-cleavage of the amyloid precursor protein (APP) and/or impaired Aβ clearance in the brain. It has been suggested that high concentrations of luteinizing hormone (LH) in women contribute to increased Aβ generation after menopause, but the mechanism for this is incompletely understood. We investigated the effect of human chorionic gonadotropin (hCG), an LH receptor agonist, on APP β-cleavage in the SH-SY5Y neuroblastoma cell line. Treatment of these cells with hCG-induced elevated β-cleavage in a dose-dependent manner: administration of 30 mIU but not 10 mIU/ml of hCG significantly increased sAPPβ levels in the cell medium 1.7-fold as measured by ELISA. These results support the notion that LH contributes to elevated Aβ levels at least in part by increasing β-cleavage of APP by β-site APP cleaving enzyme.
authors.affiliation: Brain and Mind Research Institute, School of Medical Sciences, University of Sydney, Sydney, NSW, Australia.
authors.forename: Soheila
authors.initials: S
authors.lastname: Saberi
authors.forename: Yan Ping
authors.initials: YP
authors.lastname: Du
authors.forename: MacDonald
authors.initials: M
authors.lastname: Christie
authors.forename: Claire
authors.initials: C
authors.lastname: Goldsbury
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D045744:Cell Line, Tumor; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D006063:Chorionic Gonadotropin; D012333:RNA, Messenger; D011974:Receptors, LH